| Official Name |
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/J |
| Description |
Mice homozygous for the targeted mutation, commonly referred
to as B1RB2R -/-, are viable, fertile and display no major
defects. At 4 months of age non-manipulated B1RB2R -/- mice
exhibit no significant differences in blood pressure or
kidney function when compared to Bdkrb2 deficient mice
(Stock No. 006860). Fasted B1RB2R -/- mice exhibit
significantly lower levels of plasma nitrite/nitrate
compared to Bdkrb2 deficient mice.
Post-ischemic B1RB2R -/- mice exhibit significantly higher
plasma levels of urea nitrogen and creatinine, higher levels
of oxidative nuclear and mitochondrial DNA modification, and
increased rates of apoptosis and mortality than either
wildtype or Bdkrb2 deficient mice. Histological evaluation
of the kidney indicates that post ischemic B1RB2R -/- mice
exhibit more severe histological changes in the renal
proximal tubules than either wildtype or Bdkrb2 deficient
mice (Kakoki, et al, 2007).
This Bdkrb1/Bdkrb2 targeted mutation is useful for studying
the kallikrein-kinin system, specifically the role of
bradykinin B1 receptor and bradykinin B2 receptor in
oxidative stress, mitochondrial DNA damage, apoptosis,
morphological and functional kidney changes, and other
senescence-associated phenotypes.
Mice homozygous for the targeted mutation and heterozygous
for the Ins2Akita spontaneous mutation are viable and
fertile. Similar to mice only heterozygous for the Ins2 the
double mutant mice are severely diabetic: their body weights
are 70% of wildtype, they consume over 3-fold the normal
amount of food, and their urinary output is approximately
20-fold more than that of wildtype mice. Double mutant mice
have markedly enlarged kidneys. Urinary albumin excretion in
double mutants is almost 4-fold that of either single
mutant, and double mutants experience more severe
nephropathy than mice that are heterozygous for the Akita
mutation alone. Megsin and nephrin expression is markedly
increased in double mutant mice when compared to wildtype or
to mice with either single mutation alone. By 12 months of
age, double mutant mice experience hair loss due to a
reduction in hair follicle numbers and thinning of the
dermis. Double mutants have essentially no subcutaneous fat,
severe kyphosis, reduced bone density, osteoporosis,
testicular atrophy, lipofuscin accumulation in the renal
proximal tubule and testicular Leydig cells, increased
apoptosis in the testicular seminiferous tubules and
intestinal villi, and a significantly reduced lifespan.
|